DETAILED ACTION
CONTINUED EXAMINATION UNDER 37 CFR 1.114 AFTER FINAL REJECTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission of RCE and amendment filed on October 21, 2025 have been entered. The claims pending in this application are claims 49-54 and 62-69. The objections and rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on October 21, 2025. Claims 49-54 and 62-69 will be examined.
Claim Objections
Claim 49 is objected to because of the following informalities: (1)“of perfect complementarity to” should be “perfectly complementary to”; (2) “the human genome” should be “a human genome”; (3) “of perfect complementarity to part” should be “perfectly complementary to a part”; and (4) “a sequence” in the last line should be “a sequence of the target polynucleotide sequence”.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
New Matter
Claims 49-54 and 62-69 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Newly amended independent claim 49 contains a limitation “a single-stranded probe oligonucleotide A₀ comprising a priming region, a 3’ end and a 5’ end, wherein: the 3’ end comprises a sequence of 5-50 nucleotides of perfect complementarity to a target polynucleotide sequence in the human genome”. Although the specification describes “[I]n one embodiment, the 5’ end of A0/A1 is complementary to the target across a region that is 5-50 nucleotides in length. In one embodiment, it is 5-25 nucleotides in length. In one embodiment, it is 5-20 nucleotides in length. In one embodiment, it is 5-15 nucleotides in length. In one embodiment, it is 5-12 nucleotides in length. In one embodiment, it is 5-10 nucleotides in length” (see paragraph [0080] of US 2023/0129793 A1, which is US publication of this instant case), page 4, line 20, page 9, lines 23 to 28, and Figure 15 of the specification suggested by applicant do not describe such limitation recited in claim 49 since the specification only describes that 5’ end of A0/A1 is complementary to the target across a region that is 5-50 nucleotides in length and does not describe that 3’ end of A0/A1 is complementary to the target across a region that is 5-50 nucleotides in length in the human genome.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.” MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 49, 52, 64-67, and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Fraylng et al., (WO 2017/140839 A1, published on August 24, 2017) in view of 1988 Stratagene catalog (page 39).
This rejection is different from the rejection under 35 U.S.C. 103 mailed on August 20, 2025 since the rejection on claim 49 now is based on different parts of the prior art of Fraylng et al..
Regarding claims 49, 52, and 64-67, since single-stranded oligonucleotide B can work as a padlock probe by hybridizing it’s 5’ and 3’ ends to a nucleotide sequence of human AHNAK nucleoprotein (ie., a fully complementary sequence of 5’-AGCTTGTACTGCTCC-3’) wherein the 3’ end of the single-stranded oligonucleotide B comprises a sequence 5’-CCTCG-3’ and the 5’ end of the single-stranded oligonucleotide B comprises a sequence 3’-AGCTTGTACT -5’ (see sequence alignment between 3’-AGCTTGTACT -5’ and 5’-CCTCG-3’ from 5’ and 3’ ends of single-stranded oligonucleotide B and a nucleotide sequence of human AHNAK nucleoprotein gene, 5’-AGCTTGTACTGCTCC-3’, using NCBI Blast For Nucleotide Sequence), Fraylng et al., teach a single-stranded probe oligonucleotide A0 (ie., the single-stranded first oligonucleotide B) comprising a priming region, a 3’ end, and a 5’ end, wherein the 3’ end comprises a sequence of 5-50 nucleotides (ie., 5’-CCTCG-3’) perfectly complementary to a target polynucleotide sequence (ie, the nucleotide sequence of human AHNAK nucleoprotein) in the human genome, the 5’ end comprises a sequence of 5-50 nucleotides (ie., 3’-AGCTTGTACT -5’) of perfect complementarity to part of the target polynucleotide sequence to which the 3’ end is perfectly complementary to, the priming region is between the 5’ end and the 3’ end, wherein the single-stranded probe oligonucleotide A0 is capable of hybridizing to the target nucleotide sequence in the human genome to produce a first intermediate product that comprises the 3’ end of the single-stranded probe oligonucleotide A₀; a ligase; a pyrophosphorolysing enzyme (ie., Phusion Hot Start II DNA Polymerase) capable of digesting the 3’ end of the oligonucleotide A0 in the first intermediate product; a source of ions capable of facilitating the pyrophosphorolysis reaction (ie., pyrophosphate anion); and at least one buffer, wherein digestion of the 3’ end of the oligonucleotide A₀ by the pyrophosphorolysing enzyme reveals a sequence of the target polynucleotide sequence to which the 5’ end of the probe of the oligonucleotide A₀ can hybridize as recited in claim 49, at least one deoxynucleotide triphosphates (dNTP), a polymerase (ie., Bst large Fragment DNA polymerase), and at least one buffer for the initial amplification of the target polynucleotide sequence in a sample as recited in claim 52, a phosphatase as recited in claim 64, a phosphohydrolase as recited in claim 65 (ie., pyrophosphatase is also called as pyrophosphate phosphohydrolase), a pyrophosphatase as recited in claim 66, the ligase and/or the pyrophosphorolysing enzyme (eg., Phusion Hot Start II DNA Polymerase) is thermostable (ie., stable at 37ºC or 70ºC) as recited in claim 67, and probe oligonucleotide A0 (ie., the single-stranded first oligonucleotide B) is unlabeled as recited in claim 69 (see pages 3, 11, and 12). Note that the target polynucleotide sequence and the first intermediate product are not structural limitations of claim 49.
Fraylng et al., do not disclose kits recited in claims 49, 52, 55,64-67, and 69.
1988 Stratagene catalog teaches a motivation to combine reagents into kit format (page 39).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kits recited in claims 49, 52, 64-67, and 69 by putting the single-stranded first oligonucleotide B, the enzymes, the pyrophosphate anion and the buffer taught by Fraylng et al., into a kit format in view of the prior arts of Fraylng et al., and 1988 Stratagene. One having ordinary skill in the art would have been motivated to do so because the Stratagene catalog teaches a motivation for combining reagents of use in an assay into a kit, “[E]ach kit provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. 2) The other service provided in a kit is quality control” (page 39, column 1).
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Fraylng et al., in view of 1988 Stratagene catalog as applied to claims 49, 52, 64-67, and 69 above, and further in view of Nilsen et al., (US 2008/0176233 A1, published on July 24, 2008).
The teachings of Fraylng et al., and 1988 Stratagene catalog have been summarized previously, supra.
Fraylng et al., and 1988 Stratagene catalog do not disclose that a kit further comprises positive and negative controls as recited in claim 50.
Nilsen et al., teach that “the kit may include additional components, including, for example, reagents for removing unbound label moieties, reagents for removing non-ligated detection oligonucleotides, reagents for detecting labeled small oligonucleotides, a positive control, and a negative control. The positive control may be used to assess kit components and procedure, while the negative control may be used to assess background signal(s) in tested samples” (see paragraph [0055]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kit recited in claim 50 by adding positive and negative controls into the kit recited in claim 49 in view of the prior arts of Fraylng et al., 1988 Stratagene and Nilsen et al.. One having ordinary skill in the art would have been motivated to do so because Nilsen et al., teach that “the kit may include additional components, including, for example, reagents for removing unbound label moieties, reagents for removing non-ligated detection oligonucleotides, reagents for detecting labeled small oligonucleotides, a positive control, and a negative control. The positive control may be used to assess kit components and procedure, while the negative control may be used to assess background signal(s) in tested samples” (see paragraph [0055]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kit recited in claim 50 by adding positive and negative controls into the kit recited in claim 49 in view of the prior arts of Fraylng et al., 1988 Stratagene and Nilsen et al., in order to use the positive control to assess kit components and procedure and use the negative control to assess background signals in tested samples.
Claim 51 is rejected under 35 U.S.C. 103 as being unpatentable over Fraylng et al., in view of 1988 Stratagene catalog as applied to claims 49, 52, 64-67, and 69 above, and further in view of Arnold et al., (US 2005/0042638 A1, published on February 24, 2005).
The teachings of Fraylng et al., and 1988 Stratagene catalog have been summarized previously, supra.
Fraylng et al., and 1988 Stratagene catalog do not disclose that the 5’ end of the oligonucleotide A0 is rendered resistant to 5’-3’ exonuclease digestion and the kit further comprises a 5’-3’ exonuclease as recited in claim 51.
Arnold et al., teach that a synthesized oligonucleotide containing a modification of 5’ end of the sequence that makes the oligonucleotide resistant to digestion by enzymes with 5’ exonuclease activity such as Taq DNA polymerase (see paragraphs [0027] and [0028]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kit recited in claim 51 by adding a modification resistant to digestion by enzymes with 5’-3’ exonuclease activity on 5’ end of the oligonucleotide A0 taught by Fraylng et al., during the process of synthesizing the oligonucleotide A0 and adding an enzymes with 5’ exonuclease activity such as Taq DNA polymerase to the kit recited in claim 49 in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Arnold et al.. One having ordinary skill in the art would have been motivated to do so because Arnold et al., teach that a synthesized oligonucleotide containing a modification of 5’ end of the sequence that makes the oligonucleotide resistant to digestion by an enzymes with 5’ exonuclease activity such as Taq DNA polymerase (see paragraphs [0027] and [0028]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kit recited in claim 51 by adding a modification resistant to digestion by enzymes with 5’-3’ exonuclease activity on 5’ end of the oligonucleotide A0 taught by Fraylng et al., during the process of synthesizing the oligonucleotide A0 and add an enzymes with 5’ exonuclease activity such as Taq DNA polymerase to the kit recited in claim 49 in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Arnold et al., such that the kit recited in claim 51 has a new function which has an ability to be used in an assay using an enzyme with 5’-3’ exonuclease activity wherein the oligonucleotide A0 is prevented from being cleaved by the enzyme with 5’-3’ exonuclease activity.
Claim 53 is rejected under 35 U.S.C. 103 as being unpatentable over Fraylng et al., in view of 1988 Stratagene catalog as applied to claims 49, 52, 64-67, and 69 above, and further in view of Osborne et al., (US 2017/0335371 A1, published on November 23, 2017).
The teachings of Fraylng et al., and 1988 Stratagene catalog have been summarized previously, supra.
Fraylng et al., and 1988 Stratagene catalog do not disclose that a kit further comprises a dUTP incorporating high fidelity polymerase, dUTPs, and uracil-DNA N-glycosylase (UDG) as recited in claim 53.
Osborne et al., teach that a protocol involves incorporating dUTP into a product using a DNA polymerase, and then treating the product (which contains uracil) with uracil DNA glycosylase (UDG) and an endonuclease (endonuclease IV) to fragment the product (see paragraph [0006]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kit recited in claim 53 by adding a dUTP incorporating high fidelity polymerase, dUTPs, and uracil-DNA N-glycosylase (UDG) into the kit recited in claim 49 in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Osborne et al.. One having ordinary skill in the art would have been motivated to do so because Osborne et al., teach that a protocol involves incorporating dUTP into a product using a DNA polymerase, and then treating the product (which contains uracil) with uracil DNA glycosylase (UDG) and an endonuclease (endonuclease IV) to fragment the product (see paragraph [0006]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kit recited in claim 53 by adding a dUTP incorporating high fidelity polymerase, dUTPs, and uracil-DNA N-glycosylase (UDG) into the kit recited in claim 49 in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Osborne et al., such that the kit recited in claim 53 has a new function which has an ability to be used for incorporating dUTPs to an oligonucleotide and deglycosylating uridines from an oligonucleotide.
Claim 54 is rejected under 35 U.S.C. 103 as being unpatentable over Fraylng et al., in view of 1988 Stratagene catalog as applied to claims 49, 52, 64-67, and 69 above, and further in view of Meuleman (US 2014/0349300 A1, published on November 11, 2014).
The teachings of Fraylng et al., and 1988 Stratagene catalog have been summarized previously, supra.
Fraylng et al., and 1988 Stratagene catalog do not disclose that a kit further comprises a proteinase as recited in claim 54.
Meuleman teaches that “pyrophosphorolysis can be stopped or paused by removing other reaction components. For example, polymerase can be removed from a reaction and optionally replaced or returned to an active state. For example, polymerase can be removed by fluidic, sequestration, degradation or inactivation methods such as those exemplified above for pyrophosphate. In particular embodiments, a heat sensitive (non-thermophilic) polymerase can be used in a pyrophosphorolysis reaction and then heat inactivated. Similarly, a polymerase can be degraded by chemical modification or enzymatic degradation (e.g. via a protease)” (see paragraph [0054]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kit recited in claim 54 by adding a proteinase into the kit recited in claim 49 in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Meuleman. One having ordinary skill in the art would have been motivated to do so because Meuleman teaches that “pyrophosphorolysis can be stopped or paused by removing other reaction components. For example, polymerase can be removed from a reaction and optionally replaced or returned to an active state. For example, polymerase can be removed by fluidic, sequestration, degradation or inactivation methods such as those exemplified above for pyrophosphate. In particular embodiments, a heat sensitive (non-thermophilic) polymerase can be used in a pyrophosphorolysis reaction and then heat inactivated. Similarly, a polymerase can be degraded by chemical modification or enzymatic degradation (e.g. via a protease)” (see paragraph [0054]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kit recited in claim 54 by adding a proteinase into the kit recited in claim 49 in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Meuleman such that the kit recited in claim 54 has a new function which have an ability to be used for stopping or pausing a pyrophosphorolysis reaction by removing enzymes used in the pyrophosphorolysis reaction.
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over Fraylng et al., in view of 1988 Stratagene catalog as applied to claims 49, 52, 64-67, and 69 above, and further in view of Dahl et al., (US 2017/0081702 A1, published on March 23, 2017).
The teachings of Fraylng et al., and 1988 Stratagene catalog have been summarized previously, supra.
Fraylng et al., and 1988 Stratagene catalog do not disclose that at least one single-stranded primer oligonucleotide that is substantially complementary to a portion of single-stranded probe oligonucleotide A0 as recited in claim 62. However, Fraylng et al., teach that
an amplification enzyme (ie., Bst large fragment DNA polymerase), at least one dNTP; and one or more oligonucleotide binding dyes (ie., Att0 655 dye) or molecular probes as recited in claim 62 (see pages 11 and 12).
Dahl et al., teach a kit comprising a pair of PCR primers that hybridize to the one or more probes comprising sequences X and Y (see paragraph [0136]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kit recited in claim 62 by adding at least one single-stranded primer oligonucleotide that is substantially complementary to a portion of single-stranded probe oligonucleotide A0 into the kit recited in claim 49 in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Dahl et al.. One having ordinary skill in the art would have been motivated to do so because Dahl et al., teach a kit comprising a pair of PCR primers that hybridize to the one or more probes comprising sequences X and Y (see paragraph [0136]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to add at least one single-stranded primer oligonucleotide that is substantially complementary to a portion of single-stranded probe oligonucleotide A0 into the kit recited in claim 49 in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Dahl et al., such that the kit recited in claim 62 has a new function which has an ability to be used for making a large quantity of the single-stranded probe oligonucleotide A0.
Claim 63 is rejected under 35 U.S.C. 103 as being unpatentable over Fraylng et al., in view of 1988 Stratagene catalog as applied to claims 49, 52, 64-67, and 69 above, and further in view of Fan et al., (US 2012/0202704 A1, published on August 9, 2012).
The teachings of Fraylng et al., and 1988 Stratagene catalog have been summarized previously, supra.
Fraylng et al., and 1988 Stratagene catalog do not disclose that the single-stranded probe oligonucleotide A0 is a first single stranded probe oligonucleotide A0, and the kit further comprises a second single-stranded probe oligonucleotide A0, wherein both the first single-stranded probe oligonucleotide A0 and the second single-stranded probe oligonucleotide A0 include an identification region, and the second single-stranded probe oligonucleotide A0 is complementary to a target sequence different from a target sequence to which the first single-stranded probe oligonucleotide A0 is complementary as recited in claim 63.
Fan et al., teach a kit including a first and second plurality of probe sets wherein each probe set includes a first probe having a first identification sequence and first hybridization sequence complementary to a first portion of a sequence of interest, and a second probe having a second identification sequence and a second hybridization sequence complementary to a second portion of the same sequence of interest (see paragraph [0123]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kit recited in claim 63 by adding an identical region to the first single-stranded primer oligonucleotide A0 during a process for synthesizing the first single-stranded primer oligonucleotide A0 and adding a second single-stranded primer oligonucleotide A0 comprising an identical region into the kit recited in claim 49 wherein the second single-stranded probe oligonucleotide A0 is complementary to a target sequence different from a target sequence to which the first single-stranded probe
oligonucleotide A0 is complementary in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Fan et al.. One having ordinary skill in the art would have been motivated to do so because Fan et al., teach a kit including a first and second plurality of probe sets wherein each probe set includes a first probe having a first identification sequence and first hybridization sequence complementary to a first portion of a sequence of interest, and a second probe having a second identification sequence and a second hybridization sequence complementary to a second portion of the same sequence of interest (see paragraph [0123]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to add an identical region to the first single-stranded primer oligonucleotide A0 during a process for synthesizing the first single-stranded primer oligonucleotide A0 and add a second single-stranded primer oligonucleotide A0 comprising an identical region into the kit recited in claim 49 wherein the second single-stranded probe oligonucleotide A0 is complementary to a target sequence different from a target sequence to which the first single-stranded probe oligonucleotide A0 is complementary in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Fan et al., such that the kit recited in claim 63 has a new function which has an ability to be used for identifying the first single-stranded probe oligonucleotide A0 and the second single-stranded probe oligonucleotide A0 and provides another way for identifying a target polynucleotide sequence to which the first single-stranded probe oligonucleotide A0 is complementary based on the second single-stranded probe oligonucleotide A0.
Claim 68 is rejected under 35 U.S.C. 103 as being unpatentable over Fraylng et al., in view of 1988 Stratagene catalog as applied to claims 49, 52, 64-67, and 69 above, and further in view of Chen et al., (Journal of Experimental & Clinical Cancer Research, 36, 65, published on May 12, 2017).
The teachings of Fraylng et al., and 1988 Stratagene catalog have been summarized previously, supra.
Fraylng et al., and 1988 Stratagene catalog do not disclose that the target polynucleotide sequence is in a cancer-related gene as recited in claim 68.
Chen et al., teach that AHNAK suppresses tumor proliferation and invasion by targeting multiple pathways in triple-negative breast cancer and AHNAK acts as a tumor suppressor that negatively regulates TNBC cell proliferation, TNBC xenograft growth and metastasis via different signaling pathway (see Title and Abstract).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the kit recited in claim 68 wherein the target polynucleotide sequence is in a cancer-related gene in view of the prior arts of Fraylng et al., 1988 Stratagene catalog, and Chen et al.. One having ordinary skill in the art would have been motivated to do so because the single-stranded oligonucleotide B taught by Fraylng et al., can work as a padlock probe by hybridizing it’s 5’ and 3’ ends to a nucleotide sequence of human AHNAK nucleoprotein gene (ie., a fully complementary sequence of 5’-AGCTTGTACTGC TCC-3’) wherein the 3’ end of the single-stranded oligonucleotide B comprises a sequence 5’-CCTCG-3’ and the 5’ end of the single-stranded oligonucleotide B comprises a sequence 3’-AGCTTGTACT -5’ (see sequence alignment between 3’-AGCTTGTACT -5’ and 5’-CCTCG-3’ from 5’ and 3’ ends of single-stranded oligonucleotide B and a nucleotide sequence of human AHNAK nucleoprotein, 5’-AGCTTGTACTGCTCC-3’, using NCBI Blast For Nucleotide Sequence) while Chen et al., teach that AHNAK suppresses tumor proliferation and invasion by targeting multiple pathways in triple-negative breast cancer and AHNAK acts as a tumor suppressor that negatively regulates TNBC cell proliferation, TNBC xenograft growth and metastasis via different signaling pathway (see Title and Abstract). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the kit recited in claim 68 wherein the target polynucleotide sequence is in a cancer-related gene (ie., human AHNAK nucleoprotein gene) in view of the prior arts of Fraylng et al.,1988 Stratagene catalog, and Chen et al..
Response to Arguments
Applicant’s arguments with respect to claims 49-69 have been considered but are moot because the new ground of rejection does not rely on any teaching or matter specifically challenged in the argument since the rejection on claim 49 is based on different parts of the prior art of Fraylng et al..
Conclusion
No claim is allowed.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
February 23, 2026